diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index a619238c90fdc..4bc985e02d950 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -120,6 +120,7 @@ import {
     createModuleNotFoundChain,
     createMultiMap,
     createNameResolver,
+    createPrefixSuffixTrie,
     createPrinterWithDefaults,
     createPrinterWithRemoveComments,
     createPrinterWithRemoveCommentsNeverAsciiEscape,
@@ -17669,13 +17670,55 @@ export function createTypeChecker(host: TypeCheckerHost): TypeChecker {
     }
 
     function removeStringLiteralsMatchedByTemplateLiterals(types: Type[]) {
-        const templates = filter(types, isPatternLiteralType) as (TemplateLiteralType | StringMappingType)[];
-        if (templates.length) {
+        let patterns = filter(types, isPatternLiteralType) as (TemplateLiteralType | StringMappingType)[];
+        const templateLiterals = filter(patterns, t => !!(t.flags & TypeFlags.TemplateLiteral)) as TemplateLiteralType[];
+
+        const estimatedCount = templateLiterals.length * countWhere(types, t => !!(t.flags & TypeFlags.StringLiteral));
+        // TODO(jakebailey): set higher limit after testing
+        if (estimatedCount > 0) {
+            // To remove string literals already covered by template literals, we may potentially
+            // check every string literal against every template literal, leading to a combinatoric
+            // explosion. This is made even worse if the strings all share common prefixes or suffixes,
+            // making the "fast path" of a prefix check in inferFromLiteralPartsToTemplateLiteral not actually
+            // very fast as we'll repeatedly scan the strings much farther than just a few characters.
+            //
+            // To reduce the amount of work we need to do, we can build a two-way trie out of the
+            // template literals, only checking those which can be satisfied by a given string.
+
+            const trie = createPrefixSuffixTrie<TemplateLiteralType[]>();
+
+            forEach(templateLiterals, t => {
+                const prefix = t.texts[0];
+                const suffix = t.texts[t.texts.length - 1];
+                trie.set(prefix, suffix, templates => append(templates, t));
+            });
+
+            let i = types.length;
+            outer: while (i > 0) {
+                i--;
+                const t = types[i];
+                if (!(t.flags & TypeFlags.StringLiteral)) continue;
+                const text = (t as StringLiteralType).value;
+
+                for (const templates of trie.iterateAllMatches(text)) {
+                    if (some(templates, template => isTypeMatchedByTemplateLiteralOrStringMapping(t, template))) {
+                        orderedRemoveItemAt(types, i);
+                        continue outer;
+                    }
+                }
+            }
+
+            // Fall through into the general case with just the string mappings.
+            patterns = filter(patterns, t => !!(t.flags & TypeFlags.StringMapping)) as StringMappingType[];
+        }
+
+        if (patterns.length) {
             let i = types.length;
             while (i > 0) {
                 i--;
                 const t = types[i];
-                if (t.flags & TypeFlags.StringLiteral && some(templates, template => isTypeMatchedByTemplateLiteralOrStringMapping(t, template))) {
+                if (!(t.flags & TypeFlags.StringLiteral)) continue;
+                if (some(patterns, template => isTypeMatchedByTemplateLiteralOrStringMapping(t, template))) {
                     orderedRemoveItemAt(types, i);
                 }
             }
diff --git a/src/compiler/core.ts b/src/compiler/core.ts
index fc692f1a65d2b..96a61c1066cd3 100644
--- a/src/compiler/core.ts
+++ b/src/compiler/core.ts
@@ -2590,3 +2590,96 @@ export function isNodeLikeSystem(): boolean {
         && !(process as any).browser
         && typeof require !== "undefined";
 }
+
+/** @internal */
+export interface PrefixSuffixTrie<T extends {}> {
+    iterateAllMatches(input: string): Iterable<T>;
+    set(prefix: string, suffix: string, fn: (value: T | undefined) => T | undefined): void;
+    hasAnyMatch(input: string): boolean;
+}
+
+/** @internal */
+export function createPrefixSuffixTrie<T extends {}>(): PrefixSuffixTrie<T> {
+    interface Trie<T extends {}> {
+        children: Record<string, Trie<T>> | undefined;
+        value: T | undefined;
+    }
+
+    function createTrie<T extends {}>(): Trie<T> {
+        return {
+            children: undefined,
+            value: undefined,
+        };
+    }
+
+    const root = createTrie<Trie<T>>();
+
+    function* iterateAllMatches(input: string) {
+        let node = root;
+
+        if (node.value) {
+            yield* iterateSuffix(node.value, 0);
+        }
+
+        for (let i = 0; i < input.length; i++) {
+            const child = node.children?.[input[i]];
+            if (!child) break;
+            if (child.value) {
+                yield* iterateSuffix(child.value, i + 1);
+            }
+            node = child;
+        }
+
+        return;
+
+        function* iterateSuffix(node: Trie<T>, start: number) {
+            if (node.value) {
+                yield node.value;
+            }
+
+            for (let i = input.length - 1; i >= start; i--) {
+                const child = node.children?.[input[i]];
+                if (!child) break;
+                if (child.value) {
+                    yield child.value;
+                }
+                node = child;
+            }
+        }
+    }
+
+    function set(prefix: string, suffix: string, fn: (value: T | undefined) => T | undefined) {
+        let prefixNode = root;
+
+        for (let i = 0; i < prefix.length; i++) {
+            const char = prefix[i];
+            const children = prefixNode.children ??= {};
+            const child = children[char] ??= createTrie();
+            prefixNode = child;
+        }
+
+        let suffixNode = prefixNode.value ??= createTrie();
+
+        for (let i = suffix.length - 1; i >= 0; i--) {
+            const char = suffix[i];
+            const children = suffixNode.children ??= {};
+            const child = children[char] ??= createTrie();
+            suffixNode = child;
+        }
+
+        suffixNode.value = fn(suffixNode.value);
+    }
+
+    function hasAnyMatch(input: string) {
+        for (const _ of iterateAllMatches(input)) {
+            return true;
+        }
+        return false;
+    }
+
+    return {
+        iterateAllMatches,
+        set,
+        hasAnyMatch,
+    };
+}